The past twenty years have shown a proliferation of research on both the etiology of drug use among adolescents and the effectiveness of drug prevention strategies. A large body of evidence now exists showing school-based drug abuse prevention programs that combine drug refusal skills training with techniques to enhance personal and social competence to have long-term effects on adolescent drug use. In addition, etiology research has begun to clarify how the components of effective prevention programs work. While these studies have been conducted with both white and minority populations, as well as in urban, suburban, and rural environments, few studies have examined the differential impact effective prevention programs may have on girls relative to boys. In addition, the literature shows few longitudinal studies of gender differences in the etiology of drug use. A primary goal of the proposed research is to test for gender differences in the efficacy of a proven state-of-the-art drug prevention program entitled Life Skills Training (LST). Differential effects of the program will be examined among two longitudinal samples of middle school students: a predominantly white, suburban sample (N=5,954), and a largely minority, inner-city sample (N-5,864). A secondary goal is to examine gender differences in etiological models of adolescent drug use using the untreated control students. For both studies, all 7th graders attending schools assigned to the intervention groups took part in the LST drug abuse prevention program as a part of their regular curriculum, along with booster sessions in the 8th and 9th grades. The treatment-as-usual control groups for each study did not receive any of the LST intervention. The proposed research aims to elucidate how potential mediators of program effectiveness (i.e. cognitions, attitudes, social influences, and competence) may differ by gender. Also, using the control group participants, the proposed study will examine gender differences in how risk and protective factors influence the initiation and escalation of drug use during the critical middle school years, and to examine potential mediators and moderators of this relationship. The hypothesized models will be cross-validated among ethnic subgroups of the two samples. The long-term goals are to improve understanding of both how effective prevention programs work for girls and boys and how drug use develops among girls and boys, and to use this information to improve prevention intervention programs for both genders.